The program entitled "Adhesion Molecules in Transfusion Biology" seeks to continue to conduct basic research that is relevant to major problems in Transfusion Medicine. The common theme of this program is to study adhesive interactions in the vasculature including interactions among blood cells, between normal and malignant blood cells and host endothelium or tissue, and ways these interactions affect the fate, communication and function of transfused cells. In addition to studies with human cells, all projects share a general scientific approach using genetically engineered animal models, primarily mice mutant in adhesion receptors. All projects further utilize highly sophisticated imaging techniques to visualize cellular changes and behavior in vitro and in vivo. The program is composed of four highly interactive projects. Project 1, Dr. Denisa Wagner will focus on the biology of pro-coagulant microparticle generation by P-selectin/PSGL-1 interaction from leukocytes and on the pathways emanating from platelet mitochondrial injury to the activation of ADAM17 (TACE) and platelet clearance. Project 2, Dr. John Hartwig will seek to define the mechanisms that alter the surface of refrigerated platelets and target them for removal from circulation. Project 3, Dr. Ulrich von Andrian will define how transfused dendritic cells gain access to and communicate with different subsets of bone marrow resident CDS T cells. The function of leukocyte adhesion molecules in the dissemination of multiple myeloma in the BM and the potential for transfusion-based immunotherapy will be explored. The mutant mice which are an important common resource of this program, will be housed by the Animal Care Core. Electron and multiphoton microscopy will be performed as part of the Imaging Core. We hope that the proposed basic research in cell adhesion will lead to better preservation of blood products, reduce adverse side effects, and improve the outcome of transfusions as well as lead to new immunotherapies and increase efficiency in hematopoietic stem cell engraftment.